Granulocyte colony-stimulating factor (GCSF), with or without dexamethasone, is the standard agent for mobilizing cells in granulocyte donors. The purpose of this study was to compare the effects of these agents on donors and to determine the minimum interval between donations. In this prospective, randomized, double-blinded, and placebo controlled investigation 20 donors were studied three times. Once the donors were given dexamethasone (8 mg, PO), once G-CSF (5 mg/kg SQ) and once both agents. Granulocyte concentrates were collected by apheresis 12 to 18 hours after the mobilizing agents were given. The donors were assessed and blood tests were performed before the collection, the day of the collection, and 1, 2, 7, 14, 21, 28, and 35 days after the collection. More granulocytes were collected when G-CSF was given than when was dexa-methasone was given (41.5 plus or minus 20.5 x 10 to the ninth power versus 22.2 plus or minus 11.2 x 10 to the ninth power, p less than 0.001). The most granulocytes were collected when G-CSF plus dexamethasone were given (65.6 plus or minus 24.2 x 10 to the ninth power, p less than 0.002). When dexamethasone was given, 58 percent of the donors experienced at least one symptom compared to 85 percent when G-CSF was given and 75 percent G-CSF plus dexamethasone was given. Similar proportions of donors in each group experienced fatigue (26 to 35 percent), insomnia (25 to 35 percent), and bone pain (21 to 30 percent). When G-CSF alone or with dexamethasone was given the donors experienced more headache, joint ache, nausea, diarrhea, and sore throat than when only dexamethasone was given. Following the collection, platelet counts fell and remained below baseline levels for 7 to 14 days. The hemoglobin levels also fell and remained below baseline levels for 7 to 28 days. For all three mobilization regimens the leukocyte counts returned to baseline levels within 3 to 7 days, but a mild neutropenia recurred 21 days post donation. When donors were given each of the three mobilizing regimens the following blood chemistries fell: albumin, potassium, calcium, magnesium, bilirubin, SGOT, cholesterol, and triglycerides. When donors were given dexamethasone alone or dexamethasone plus G-CSF, sodium, chloride, and glucose levels rose, but bicarbonate and creatinine levels fell. Calcium, uric acid, and triglycerides levels did not return to baseline levels until 21 days following the collection; albumin, bilirubin, and SGOT until 28 days; and cholesterol, until 35 days after the collection. The administration of G-CSF plus dexamethasone results in greater granulocyte concentrate yields, and causes no more symptoms than G-CSF alone. The administration of all three mobilization regimens and the collection of granulocyte concentrates caused mild changes in blood counts and blood chemistries for up to 28 days after the collection. At least 4 weeks should separate donations to allow blood counts and chemistries to return to baseline levels.